The present invention relates to bioreactors for performing biological and/or biochemical reactions. More specifically, the present invention relates to a bioreactor for culturing cells (e.g., biological samples) and for use in the production of medical materials such as hormones, enzymes, antibodies, vaccines, and drugs. The invention further relates to an improved bioreactor that is easy to assemble and maintains sterility throughout the culturing/fermentation operation, and provides for sterile transfer of material to larger vessels.
In the medical field, it is often necessary to cultivate biological samples for further study of cell structures. Such culturing is often carried out in a bioreactor, which is essentially a sterile vessel that provides internal sealed conditions suitable for cell growth. Bioreactors are also used in the production of medical materials such as hormones, enzymes, antibodies, vaccines, and drugs. Typically, the bioreactor produces batch quantities of the desired material to “seed” larger vessels for further processing. These larger vessels are essentially large bioreactors, which continue the culturing/production process. The “smaller” bioreactors are used to produce an effective amount of material of sufficient concentration such that the material can continue culturing/fermentation in the larger vessel. The larger bioreactor vessels have the increased capacity necessary to produce increased quantities of the desired material for study purposes or for further processing into a final product such as a vaccine or drug. The smaller bioreactors, which feed larger vessels, are limited in production capability because, for a given amount of reaction medium introduced into the smaller bioreactor, the bioreactor can generate only a finite amount of product. As a result, transfer of a “seed” product to a larger vessel is necessary for further production.
Generally, three basic types of bioreactors are used in the medical field for producing biological and/or biochemical reactions, namely, a stationary type, a shaking type, and a rotating type. In stationary bioreactors, a fixedly settled reaction vessel, such as an Erlenmeyer flask, is employed in which a stirrer is provided and which operates to produce a generally horizontal rotary movement to cause agitation of the reaction mixture. This stirring action increases the heat transfer and oxygen transfer rate. While this type of bioreactor permits economical running of reactions, it typically cannot operate with a highly viscous substrate due to insufficient driving torque of the stirrer, and the heat and oxygen transfer are mass transfer limited. In this type of bioreactor, substrates with densities different from that of the solvent, (i.e., the reaction medium), tend to float up or settle down which causes separation of the reaction mixture.
In shaking type bioreactors, a shaking culture using test tubes as the culture vessel has been widely used in the medical field. In this type of system, the reaction is accelerated by reciprocating horizontal movement of the culture vessel. This type of bioreactor also does not operate well with highly viscous mediums and also suffers the same mass transfer and separation problems as the stationary type bioreactor discussed previously.
Rotating type bioreactors are most commonly used in the medical field. In rotating bioreactors, the reaction medium is subjected to agitation by a rotating apparatus inserted into the vessel. An example of a rotating bioreactor is disclosed in U.S. Pat. No. 5,587,298 to Horigane et al. This patent discloses a bioreactor comprised of a reaction vessel defining a reaction chamber which is surrounded by a water jacket for maintaining a predetermined constant temperature. The reaction chamber is provided in the vicinity of the inner wall surface of the reaction vessel. A pair of upright screws is disposed in a side-by-side and adjoining relationship and is used to agitate the reaction mixture. In particular, each screw has a screw thread or a helical fin which engages the corresponding screw thread on the adjacent screw to introduce agitation into the reaction mixture. The reaction mixture is subjected to uniform agitation and to a milling and sieving action in the area where the screw threads are engaged.
Another example of a rotating bioreactor is disclosed in U.S. Pat. No. 4,636,675 to Freedman et al. This patent discloses, in particular, an improved agitator for a bioreactor vessel. The agitator includes a hollow body assembly having an open end and a closed end and a tubular structure communicating with the hollow body assembly at a location spaced from the open end. The tubular structure has an exit opening oriented such that rotational movement of the agitator and the tubular structure causes a suction or draft at the exit opening to cause flow of fluid from the open end of the hollow body assembly through the hollow body assembly and out through the tubular structure exit opening. The agitator is driven by a magnetic drive motor.
Another example of a rotating bioreactor is disclosed in U.S. Pat. No. 4,636,675 to Freedman et al. This patent discloses, in particular, an improved agitator for a bioreactor vessel. The agitator includes a hollow body assembly having an open end and a closed end and a tubular structure communicating with the hollow body assembly at a location spaced from the open end. The tubular structure has an exit opening oriented such that rotational movement of the agitator and the tubular structure causes a suction or draft at the exit opening to cause flow of fluid from the open end of the hollow body assembly through the hollow body assembly and out through the tubular structure exit opening. The agitator is driven by a magnetic drive motor.